Use of adenosine, hypoxanthine and ribose-containing solution for improved protection of the heart during surgery

Abstract

The invention relates to an improved cardioplegic solution for reducing ischemic damage to the heart during operations and/or transplantation. The invented solution contains adenosine, hypoxanthine and ribose in addition to the electrolytes contained in standard cardioplegic solutions.

We claim: 
     
       1. A heart perfusate for reducing ischemic damage to a heart isolated from a normal blood supply comprising a cardioplegic solution having at least one purine nucleoside additive. 
     
     
       2. The cardioplegic solution of claim 1 wherein the additive is adenosine. 
     
     
       3. The cardioplegic solution of claim 1 wherein the additive is adenosine in a final concentration in the solution of about 100 μmoles per liter. 
     
     
       4. The cardioplegic solution of claim 1 wherein the additive is hypoxanthine. 
     
     
       5. The cardioplegic solution of claim 1 wherein the additive is hypoxanthine in a final concentration in the solution of about 100 μmoles per liter. 
     
     
       6. The cardioplegic solution of claim 1 and a sugar additive, wherein the sugar additive is ribose. 
     
     
       7. The cardioplegic solution of claim 1 and a sugar additive, wherein the sugar additive is ribose in a final concentration in the solution of about 2 mmolar. 
     
     
       8. The cardioplegic solution of claim 1 wherein the additive is adenosine, hypoxanthine and ribose. 
     
     
       9. The cardioplegic solution of claim 1 wherein the additive is adenosine in a final concentration in the solution of about 100 μmoles per liter, hypoxanthine in a final concentration in the solution of about 100 μmoles per liter, and ribose in a final concentration in the solution of about 2 mmoles per liter. 
     
     
       10. The cardioplegic solution of claim 1 wherein the additive is adenosine ina final concentration in the solution of about 100 μmoles per liter, hypoxanthine in a final concentration in the solution of about 100 μmoles per liter, and ribose in a final concentration in the solution of about 2 mmoles per liter, further comprising Na, Cl, K, Ca and Mg ions in solution. 
     
     
       11. The cardioplegic solution of claim 1 wherein the additive is adenosine in a final concentration in the solution of about 100 μmoles per liter, hypoxanthine in a final concentration in the solution of about 100 μmoles per liter, and ribose in a final concentration in the solution of about 2 mmoles per liter, further comprising Na, Cl, K, Ca and Mg ions in solution in the following approximate concentrations:   ______________________________________                                    
       Na          110    meq/1                                           
       Cl          160    meq/1                                           
       K           16     meq/1                                           
       Ca.sup.++   2.4    meq/1                                           
       Mg          32     meq, and                                        
       NaHCO.sub.3 or HCl to adjust pH to 7.4.                            
______________________________________                                    
     
     
     
       12. An improved method for enhancing ability of a myocardium to tolerate ischemia comprising perfusing a preischemic heart with a cardioplegic solution containing at least one purine nucleoside during either cardiovascular surgery or harvesting for cardiac transplantation, wherein the cardioplegic solution reduces the rate of ATP degradation during ischemia. 
     
     
       13. The method of claim 12 wherein the purine nucleoside is adenosine. 
     
     
       14. The method of claim 12 wherein the purine nucleoside is hypoxanthine. 
     
     
       15. The method of claim 14 further comprising perfusing the heart with a solution containing ribose. 
     
     
       16. The method of claim 12 wherei the at least one purine nucleoside is adenosine and hypoxanthine and wherein the solution further contains ribose.